Mapping Signal Transduction with mTOR Antibodies

Thu, 06/21/2012 - 13:00

The protein encoded by mTOR (mammalian target of rapamycin), also known as dTOR in Drosophila, belongs to a family of phosphatidylinositol kinase-related kinases. These kinases regulate fundamental processes of cell growth, proliferation, metabolism

, and migration. mTOR is the target for the cell-cycle arrest and immunosuppressive effects of the drug rapamycin. Deregulation of mTOR stimulates an environment favorable for tumor development and progression. mTOR knockout mice are embryonic lethal. Using mTOR antibodies, researchers have shown that mTOR is required for the maturation and differentiation of multiple cell lineages in a mouse knock-in system (1).

The signal transduction pathways linked to mTOR have been extensively mapped. An mTOR antibody was used to show that PKB (protein kinase B) directly phosphorylates mTOR (2). Certain aspects of TOR signaling are conserved between yeast and mammals as evidenced by immunoprecipitation studies with an mTOR antibody (3). A novel MTOR binding partner, PRAS40 (proline-rich Akt/PKB substrate 40 kDa) appears to mediate signaling in an insulin-dependent manner (4). As a downstream target for the PI3K and Akt pathways, significant research has gone into targeting mTOR signaling in cancer. Specifically, Marinov, et al. review the lack of success in targeting mTOR in lung cancers (5), Jazirehi, et al. review the successes of combinatorial therapy using PI3K/Akt/TOR inhibitors in Phase I and II clinical trials for melanoma (6), and Barnett discusses the promising results of the mTOR inhibitor drug everolimus in Phase III studies of breast cancer subtypes (7).